Pre-ischemic Lactate Levels Affect Post-ischemic Recovery in an Isolated Rat Heart Model of Donation After Circulatory Death (DCD)

Copyright © 2021 Arnold, Segiser, Graf, Méndez-Carmona, Sanz, Wyss, Kalbermatter, Keller, Carrel and Longnus..

Introduction: Donation after circulatory death (DCD) could substantially improve donor heart availability. In DCD, the heart is not only exposed to a period of warm ischemia, but also to a damaging pre-ischemic phase. We hypothesized that the DCD-relevant pre-ischemic lactate levels negatively affect the post-ischemic functional and mitochondrial recovery in an isolated rat heart model of DCD. Methods: Isolated, working rat hearts underwent 28.5' of global ischemia and 60' of reperfusion. Prior to ischemia, hearts were perfused with one of three pre-ischemic lactate levels: no lactate (0 Lac), physiologic lactate (0.5 mM; 0.5 Lac), or DCD-relevant lactate (1 mM; 1 Lac). In a fourth group, an inhibitor of the mitochondrial calcium uniporter was added in reperfusion to 1 Lac hearts (1 Lac + Ru360). Results: During reperfusion, left ventricular work (heart rate-developed pressure product) was significantly greater in 0.5 Lac hearts compared to 0 Lac or 1 Lac. In 1 vs. 0.5 Lac hearts, in parallel with a decreased function, cellular and mitochondrial damage was greater, tissue calcium content tended to increase, while oxidative stress damage tended to decrease. The addition of Ru360 to 1 Lac hearts partially abrogated the negative effects of the DCD-relevant pre-ischemic lactate levels (greater post-ischemic left ventricular work and less cytochrome c release in 1 Lac+Ru360 vs. 1 Lac). Conclusion: DCD-relevant levels of pre-ischemic lactate (1 mM) reduce contractile, cellular, and mitochondrial recovery during reperfusion compared to physiologic lactate levels. Inhibition of mitochondrial calcium uptake during early reperfusion improves the post-ischemic recovery of 1 Lac hearts, indicating calcium overload as a potential therapeutic reperfusion target for DCD hearts.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:8

Enthalten in:

Frontiers in cardiovascular medicine - 8(2021) vom: 26., Seite 669205

Sprache:

Englisch

Beteiligte Personen:

Arnold, Maria [VerfasserIn]
Segiser, Adrian [VerfasserIn]
Graf, Selianne [VerfasserIn]
Méndez-Carmona, Natalia [VerfasserIn]
Sanz, Maria N [VerfasserIn]
Wyss, Rahel K [VerfasserIn]
Kalbermatter, Nina [VerfasserIn]
Keller, Nino [VerfasserIn]
Carrel, Thierry [VerfasserIn]
Longnus, Sarah [VerfasserIn]

Links:

Volltext

Themen:

Cardiac ischemia reperfusion injury
Contractile function
Donation after circulatory death
Heart transplantation
Journal Article
Lactate

Anmerkungen:

Date Revised 02.07.2021

published: Electronic-eCollection

Citation Status PubMed-not-MEDLINE

doi:

10.3389/fcvm.2021.669205

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM327420065